Since the early 1970s, the electronics industry has been essentially identified with metal-oxide semiconductor (MOS) large-scale integrated circuits. During the past decades, remarkable advances have been accomplished by the downsizing of components (such as MOS field-effect transistors), and the number of transistors on a chip has continuously increased in accordance with Moore's law thanks to constant improvements in lithographic resolution (the top±down approach). However, this approach is unlikely to be sustainable due to intrinsic physical limitations and to the vast increase in production costs. Molecular electronics was proposed in 1974 by Aviram and Ratner [1] as an alternative bottom±up approach for either standard devices (such as diodes and transistors) or new functional devices. It aims to exploit the unique features of molecular systems, such as the high reproducibility and small size of the building blocks, thermodynamically driven self-assembly, and self-recognition. Today, the obstacles to the development of molecular electronics devices appear more technical than conceptual; [2±4] the main problems are the development of reliable methods to interconnect molecules, to characterize and understand their electronic properties, and to exploit them in real devices. In this work, we take advantage of the redox properties and the functional groups of a protein, blue-copper azurin, to achieve a hybrid transistor based on proteins covalently bonded in ordered layers onto Si/SiO 2 substrates. This is a different and innovative approach with respect to those based on physisorbed monolayers obtained by evaporation or spincoating, or based on single nanosized objects like carbon nanotubes that have serious interconnection problems.[5] The integrity of proteins in dry monolayers is investigated by intrinsic fluorescence spectroscopy, and a model for transport due to the novelty of the material is also proposed. Azurin from P. aeruginosa (Fig. 1b, inset) is a 14.6 kDa blue-copper protein that, in vitro, is able to mediate electron transfer (ET) from cytochrome c 551 to nitrite reductase from the same organism.[ ) is located at one end of the b-barrel-structure protein and at a distance of » 2.6 nm from the copper site. [8] It allows the chemisorption of azurin in oriented monolayers onto crystalline gold or other suitably functionalized surfaces. [9,10] Our prototype structure (Fig. 1a) is a planar metal±insula-tor±metal nanojunction, consisting of two Cr/Au (6 nm thick Cr layer under a 35 nm thick Au layer) arrow-shaped metallic electrodes facing each other at the oxide side of a Si/SiO 2 substrate (drain and source electrodes) and connected by the self-assembled protein monolayer.[11] The nanojunction was fabricated by electron-beam lithography, [12] and a silver gate electrode was deposited on the back of the p-doped Si substrate to form an ohmic bond acting as the back gate in a field-effect transistor (FET) configuration. Both the source± drain separation and the oxide thickness were 100 nm. Typically, aft...